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Title 

Hypoxic microenvironmental control of stress protein and erythropoietin gene expression

Authors 

Sun Hee BaekMi Young HanSeung Hoon LeeEun Mi ChoiYoung Mee Park

Publisher 

Springer Verlag (Germany)

Issue Date 

1999

Citation 

Journal of Biochemistry and Molecular Biology, vol. 32, no. 2, pp. 112-118

Keywords 

AngiogenesisErythropoietinHeat shock proteinHypoxiaSolid tumor

Abstract 

The presence of hypoxic cells in solid tumors has long been considered a problem in cancer treatment such as in radiation therapy or treatment with some anticancer drugs. It has been suggested that hypoxic cells are involved in the development of a more aggressive phenotype and contribute to metastasis. In this study, as an attempt to understand how tumor cells adapt to hypoxic stress, we investigated the regulation of the hypoxia-induced expression of proteins that control essential processes of tumor cell survival and angiogenesis. We first examined whether hypoxia induces stress protein gene expression of murine solid tumor RIF cells. We also examined hypoxia-induced changes in angiogenic gene expression in these cells. Finally, we investigated the association of the elevated levels of stress proteins with the regulation of hypoxia-induced angiogenic gene expression. Results demonstrated that hypoxia induced the expression of the erythropoietin (EPO) gene and at least two major members of stress proteins, heat shock protein 70 (HSP70) and 25 (HSP25) in RIF tumor cells. Evidence that the expression of EPO gene was greatly potentiated in TR cells suggested that the elevated levels of HSPs may play an important role in the regulation of the hypoxia-induced EPO gene expression. One of the RIF variant cell lines, TR, displays elevated levels of HSPs constitutively. Taken together, our results suggest that a hypoxic tumor microenvironment may promote the survival and malignant progression of the tumor cells by temporarily increasing the level of stress proteins and expressing angiogenic genes. We suspect that stress proteins may be associated with the increase of the angiogenic potential of tumor cells under hypoxia.

ISSN 

1225-8687

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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